Is the balance between nitric oxide and superoxide altered in spontaneously hypertensive rats with endothelial dysfunction?

Background. Increases in oxidant stress, i.e. excessive production of super oxide anion (.O-2(-)), have been reported in different models of hypertensi on. This study was-designed to test the hypothesis that increased .O-2(-) p roduction, more than diminished nitric oxide (NO) generation, plays a criti cal role in endothelial dysfunction present in spontaneously hypertensive r ats (SHR). Methods. The study was performed in 30-week-old normotensve Wistar-Kyoto ra ts (WKY) and SHR. In addition, 16-week-old SHR were treated with oral irbes artan (average dose 20 mg/kg per day) for 14 weeks (SHR-I). Aortic nicotina mide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH /NADPH) oxidase activity was determined, by-use of chemiluminescence with l ucigenin. Aortic constitutive nitric oxide synthase (cNOS) activity:was det ermined by measuring the conversion of L-arginine to L-citrulline. Vascular responses to acetylcholine were determined by isometric tension studies. Results. Whereas systolic blood pressure (SBP) was significantly increased in SHR compared with WKY, no differences were observed in SEP between SHR-I and WKY. In SHR compared with WKY, we found significantly greater NADH/NAD PH-driven .O-2(-) production, similar cNOS-mediated NO production and an im paired vasodilation in response to acetylcholine. Treated SHR had similar N ADH/NADPH oxidase activity and significantly lower cNOS activity than the W KY group. Vasodilation in response to acetylcholine was improved in SHR-I. Conclusions. These findings suggest that a diminished availability of NO se condary to an enhanced NADH/ NADPH oxidase-dependent .O-2(-) production may play a critical role in endothelial dysfunction of adult SHR.